Addictions and the associated public health problems of HIV transmission, crime and violence, exact a severe toll on our nation, costing billions annually in health care, lost productivity, and incarceration. As there have been rapid advances in neuroscience and genetics in the past two decades, we need to speed the forward translation of this knowledge into more effective clinical treatments for the addictions. Conversely, for addiction treatments with some known efficacy, we can now apply new neuroscience and genetic tools in backward- translation -- e.g., finding why a treatment works well for some individuals, yet not at all for others. To help meet the need for skilled translational researchers, this application proposes continuation of a successful (17 total trainees; 13 in the current funding period) NIDA T32 Translational Addiction Research Fellowship at the University of Pennsylvania. The (pre- and postdoctoral) training program make explicit a long-standing translational tradition at Penn, integrating clinical and basic research strengths to create trainees, whether clinical or preclinical, Ph.D.s or M.D.s, who will accelerate addiction science in the next decade. The emphasis on translation is reflected at each level of the program - through the Co-PIs (clinical and basic, Drs. Childress and Pierce), the internal and external advisory board members, the formal didactics, the dual (clinical - preclinical) mentoring, and in the trainees' mentored research projects. The translational emphasis of the program is driven by the recognition that addictions are complex disorders, multi-determined by interaction of genetic vulnerabilities, exposure to drug, and a host of modulating (e.g., early trauma ,stress, cultural norms) influences. Trainees are thus offered state-of-the-art knowledge about these interacting determinants through a didactic series specific to the program, and through mentored projects that may range from molecular and genetic studies, to brain systems (neuroscience and neuroimaging), to clinical treatment trials, and drug policy. This wide range of choices is enabled by the long history of excellence in addiction research at the University, reflected in the several academic research Centers (Penn Center for Studies on Addiction; Translational Research Laboratories/CNB; Center for AIDS Research; Center for Integrated Nicotine Research (CIRNA), the Treatment Research Institute, and collaborative laboratories offering skilled, successful mentors to the Fellowship. Mentored research also takes place within several affiliated treatment settings (VA, Presby-Penn, community methadone clinics, and mobile HIV Prevention units), critical for translating new research findings into the real world?.